Presentation on theme: "The Use of Topical Flurbiprofen Cream to Treat Plantar Fasciitis, a Randomized, Prospective Trial vs Oral NSAID Therapy Jeffery Alexander, DPM FACFAS Rush."— Presentation transcript:
The Use of Topical Flurbiprofen Cream to Treat Plantar Fasciitis, a Randomized, Prospective Trial vs Oral NSAID Therapy Jeffery Alexander, DPM FACFAS Rush University Medical Center Chicago, IL
Plantar Fasciitis Most common cause of plantar heel pain Affects up to 10% of US population Accounts for >600,000 patient visits annually in the US
Plantar Fasciitis Inflammation and pain along the plantar fascia - the tissue band that supports the arch on the bottom of the foot Pain is usually found on the bottom of the heel at the point where the plantar fascia attaches to the heel bone Becomes chronic in 5-10% of all patients Is not necessarily associated with a heel spur Over 90% resolve with conservative treatment
Plantar Fasciitis Symptoms Pain on standing, especially after periods of inactivity or sleep Pain subsides after a period of time, returns with activity after rest (post static dyskinesia) Pain related to footwear – can be worse in flat shoes with no support Radiating pain to the arch and/or toes In later stages, pain may persist/progress throughout the day Pain varies in character: dull aching, “ bruised ” feeling. Burning or tingling, numbness, or sharp pain, may indicate local nerve irritation
Plantar Fasciitis Risk Factors Biomechanical abnormalities Overly tight calf muscle Poor shoe choices Weight gain Barefoot walking Work surface
Plantar Fasciitis Treatment- Overview Mechanical – treat the cause Anti-inflammatory – treat the pain Neither done in isolation
Plantar Fasciitis Treatment Stretching, shoe modifications, avoid walking barefoot Icing and rest Night or resting splint Supplemental arch support (OTC vs. custom orthotics) Anti-inflammatory medication Steroid injections Physical therapy If conservative measures fail, surgery is an option
Other options for heel pain Over 90% of heel pain patients respond to initial therapies within a relatively short period of time For unresponsive cases, options include: – Minimally invasive procedures like ESWT (Extracorporeal Shock Wave Therapy) – Autologous Platelet Concentrate (APC) injection – Surgical procedures, open or endoscopic – Cryosurgery – Radiofrequency techniques
What Does Research Tell Us About Treatment? Approximately 80% of patients treated conservatively had complete resolution of their symptoms 1 No evidence strongly supports the effectiveness of any treatment for plantar fasciitis Cochrane Review 2 showed corticosteroid injections improved plantar fasciitis symptoms at one month but not at six months when compared to placebo
Research Specific to NSAIDs and Plantar Fasciitis Treatment protocols in most studies include ice and NSAID therapy. No studies have specifically examined their effectiveness. 3 Although no data supports the use of NSAIDs or ice, their effectiveness in managing other musculoskeletal conditions makes them reasonable choices for adjunctive therapy 4 5
Complications of Oral NSAID Use High incidence events – GI disturbances Nausea, Vomiting, Dyspepsia Potential Serious Events – GI ulceration or bleeding – Hypertension – Cardiovascular events – Acute renal impairment – Hepatotoxicity
Oral NSAIDs - Cost of Adverse Events In 1983, it cost an estimated $8.6 billion to treat arthritis in the USA It cost an additional $3.9 billion to treating gastrointestinal side effects of NSAIDs for a total cost of 12.5 billion. Conclusion: 30% of medical costs when using oral NSAIDs can be attributed to gastrointestinal side effects.
Are Oral NSAIDs Still the Answer? The authors sought to determine if alternative therapies could offer equal efficacy with improved side effect profile With advancements in available transdermal carrier agents, topical NSAID formulations were selected
Background Topical anti-inflammatories 7,9 : – Advantages: Little to no systemic absorption, no GI upset, considered safe for renally impaired, good for patients that do not want to take more medications. – Disadvantages: Application can be difficult (locations and flexibility of patient), cost, variability in penetration/absorption. Recent study showed significantly higher concentrations of flurbiprofen in tendon, muscle and periosteal tissues when administered through a patch vs. oral, however, there was a large degree of variability between individuals. 8 Purpose: Determine if topical anti-inflammatories can be an equally effective alternative to oral NSAIDs. 14
Effect of Compounded Topical Anti- Inflammatory Cream (Flurbiprofen) vs PO NSAID (Ibuprofen) in the Treatment of Plantar Fasciitis- A Pilot Study Jeffey Alexander, DPM Gene Choi, DPM
Methods Power analysis, study designed to be a non-inferiority study 60 patients with unilateral plantar fasciitis were randomized into 2 groups: (40 experimental, 20 control) – Exclusion criteria: Previous professional treatment, suspicion of nerve involvement (+ tinels/valleix sign, tarsal tunnel syndrome), contralateral pain, h/o NSAID intolerance (GI upset, hypersensitivity), renal impairment, CV disease, cortisone injections, failure to comply. – Inclusion criteria: Symptomatic for > 4 weeks and not resolving. – Age: ranged from 29 – 79 (Avg: Experimental 55.7, Control 59.5) All patients instructed to reduce activity, ice (20min 3x/day), perform stretching exercises (written and visual instructions), and use standard OTC orthotics.
Methods Experimental group: Compounded topical anti- inflammatory medication containing: Flurbiprofen 10%, Baclofen 2% and Lidocaine 5% in a Lipoderm base with pentoxifylline 3%. Control group: Ibuprofen 800mg PO TID Record weekly pain scores using VAS Follow up weekly for 3 months.
Data Patients ’ weekly pain scores were rated using the visual analog pain scale (VAS) on initial visit and subsequent weekly follow up visits. Experimental group: – Avg: 4.3667 point decrease in pain. (σ: 1.846) – Avg: 65.3% (0.6526) relief in pain (σ: 0.1945) Control group: – Avg: 3.6 point decrease in pain. (σ: 0.5477) – Avg: 60.9% (0.6086) relief in pain (σ: 0.1132) Reported adverse events – Topical: Texture complaints (2/40) – Oral: GI Upset (4/20)
Statistics F-test: % Change in VAS – P = 0.30559 – Accept H o : No significant difference between oral vs. topical. F-test: Mean differences in VAS – P = 0.03052 – Reject H o : Topical significantly better relief than oral. 19 F-Test Two-Sample for Variances (CI=95%) Descriptive Statistics: Using Mean differences VARControlExperimental Sample size 2040 Mean 3.64.36667 Variance 0.33.40952 Standard Deviation 0.547721.84649 Mean Standard Error 0.244950.47676 Summary F 11.36508 F Critical value (5%) 5.87335 p-level 1-tailed 0.01526 p-level 2-tailed 0.03052 H0 (5%)?rejected F-Test Two-Sample for Variances (CI=95%) Descriptive Statistics: Using % differences VARControlExperimental Sample size2040 Mean0.608570.65264 Variance0.012820.03781 Standard Deviation0.113210.19446 Mean Standard Error0.050630.05021 Summary F2.95047F Critical value (5%)5.87335 p-level 1-tailed0.1528p-level 2-tailed0.30559 H0 (5%)?accepted
Statistics ANOVA: Mean differences in VAS – P = 0.37977 – Accept H o : No significant difference between oral vs. topical. ANOVA: % Change in VAS – P = 0.64041 – Accept H o : No significant difference between oral vs. topical. 20 Analysis of Variance (One-Way) CI=95% Using Mean differences Summary Groups Sample sizeSumMeanVariance Experimental 4065.54.366673.40952 Control 2018.3.60.3 ANOVA Source of VariationSSdfMSFp-levelF crit Between Groups2.204171 0.81080.379774.41387 Within Groups48.93333182.71852 Total 51.137519 Analysis of Variance (One-Way) CI=95% Summary Groups Sample sizeSumMeanVariance Experimental 409.789580.652640.03781 Control 203.042860.608570.01282 ANOVA Source of VariationSSdfMSFp-levelF crit Between Groups0.007281 0.225740.640414.41387 Within Groups0.58066180.03226 Total 0.5879519
Statistics T-test: Mean differences in VAS – P = 0.16975 – Accept H o : No significant difference between oral vs. topical. T-test: % Change in VAS – P = 0.54811 – Accept H o : No significant difference between oral vs. topical. 21 Comparing Means [ t-test assuming unequal variances (heteroscedastic) ] Descriptive Statistics: Using Mean differences VARSample sizeMeanVariance 404.366673.40952 203.60.3 Summary Degrees Of Freedom 18 Hypothesized Mean Difference 0.E+0 Test Statistics 1.43033 Pooled Variance 2.71852 Two-tailed distribution p-level 0.16975 t Critical Value (5%) 2.10092 One-tailed distribution p-level 0.08488 t Critical Value (5%) 1.73406 Pagurova criterion Test Statistics 1.43033 p-level 0.83023 Ratio of variances parameter 0.79116 Critical Value (5%) 0.06359 Comparing Means [ t-test assuming unequal variances (heteroscedastic) ] Descriptive Statistics: Using % differences VARSample sizeMeanVariance 400.652640.03781 200.608570.01282 Summary Degrees Of Freedom12Hypothesized Mean Difference0.E+0 Test Statistics0.61802Pooled Variance0.03226 Two-tailed distribution p-level0.54811t Critical Value (5%)2.17881 One-tailed distribution p-level0.27406t Critical Value (5%)1.78229 Pagurova criterion Test Statistics0.61802p-level0.45089 Ratio of variances parameter0.49584Critical Value (5%)0.06414
Results Topical compounded anti-inflammatory cream with flurbiprofen is NON INFERIOR to oral NSAIDs in treating plantar fasciitis. Adverse Events: – Topical Cream: 5% (2/40) complained that the cream was “ sticky ” (1/40) or “ gritty ” (1/40), but both of these patients continued to use it because of the efficacy – Oral NSAID: 20% (4/20) with GI Upset, but none of these patients discontinued therapy
Where Does the NSAID Go? 6 Oral vs. Topical NSAID Comparison of Median Maximum Concentrations, cMax, of NSAID in Joint Tissue after Topical and Oral Administration NSAID is Maximized in Cartilage and Meniscus and Minimized in Plasma After Topical Application Rolf C, et al. Intra-articular absorption and distribution of ketoprofen after topical plaster application and oral intake in 100 patients undergoing knee arthroscopy. Rheumatology (1999); 38:564-567.
What about Flurbiprofen and Plantar Fasciitis? Better penetration into soft tissues in topical formulations than oral 8 – All percents are tissue:plasma concentrations Tendon Oral 7% Topical 160% Muscle Oral 3% Topical 77% Periosteum Oral 9% Topical 65% Bone Oral 4% Topical 11% 8 Kai S, Kondo E, Kawaguchi Y, et al. Flurbiprofen concentration in soft tissue is higher after topical application than after oral administration. British J Clinical Pharm. 2012. 75:3;799-804.
Advantages of Topicals Improved Safety Profile Avoids GI 1 st pass metabolism – Traditionally 25% GI side effects using PO NSAIDs Most topical components do not reach systemic levels – Finch et al (2009)- Ketamime levels were below detectable limits – ME Lynch et al (2003)- Blood levels showed no significant absorption of Amitriptyline or Ketamime – No specific absorption of either agent after 7 days of treatment – 15% of topical NSAIDs is thought to be absorbed systemically
Discussion Limitations: – Small sample size, unable to appreciate safety advantages of topical formulations. – Limited follow up. Future research: Blinded prospective study comparing the topical compound cream with a placebo cream.
References 1 Wolgin M, Cook C, Graham C, Mauldin D. Conservative treatment of plantar heel pain: long term follow up. Foot Ankle Int. 1994:15:97-102. 2 Crawford F, Thomson C. Interventions for treating heel pain. Cochrane Database Syst Rev. 2003;(3):CD000416. 3 Buchbinder R. Clincal Practice. Plantar Fasciitis. New Engl J Med. 2004;350:2159-66. 4 Pfeffer G, Bacchetti P, Deland J, Lewis A, Anderson R, Davis W. Comparison of custom and prefabricated orthoses in the initial treatment of proximal plantar fasciitis. Foot Ankle Int. 1999;20:214-21. 5 DiGiovanni BF, Nawoczenski DA, Lintal ME, Moore EA, Murray JC, Wilding GE, et al. Tissue-specific plantar fasciastretching exercise enhances outcomes in patients with chronic heel pain. A prospective, randomized study. J Bone Joint Surg Am. 2003;85-A:1270-7. 6 Rolf C, et al. Intra-articular absorption and distribution of ketoprofen after topical plaster application and oral intake in 100 patients undergoing knee arthroscopy. Rheumatology (1999); 38:564-567.
Referenced 7 Jorge LL, Feres CC, Teles VE. Topical preparations for pain relief: efficacy and patient adherence. J Pain Research. 2011. 4;11-24. 8 Kai S, Kondo E, Kawaguchi Y, et al. Flurbiprofen concentration in soft tissue is higher after topical application than after oral administration. British J Clinical Pharm. 2012. 75:3;799-804. 9 Pandey MS, Belgamwar VS, Surana SJ. Topical delivery of flurbiprofen from pluronic lecithin organogel. Indian J Pharm Sci. 2009. 71;87-90. 10 Dexter F, Chestnut DH. Analysis of statistical tests to compare visual analog scale measurements among groups. Anesthesiology. 1995. 82:896-902.